Combinatorial lipid-nanosystem for dermal delivery of 5-fluorouracil and resveratrol against skin cancer: Delineation of improved dermatokinetics and epidermal drug deposition enhancement analysis
Autor: | Meher Rizvi, Ashif Iqubal, Mohammad Kashif Iqubal, Sanjula Baboota, Khalid Imtiyaz, Javed Ali, Madan Mohan Gupta |
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Rok vydání: | 2021 |
Předmět: |
Drug deposition
Skin Neoplasms Cell Survival Drug Compounding Skin Absorption Pharmaceutical Science Antineoplastic Agents 02 engineering and technology Resveratrol Administration Cutaneous 030226 pharmacology & pharmacy Excipients 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dermis Cell Line Tumor medicine Animals Humans Tissue Distribution Particle Size Skin Drug Carriers Epidermis (botany) General Medicine Permeation 021001 nanoscience & nanotechnology medicine.disease Lipids In vitro Rats Drug Combinations Drug Liberation medicine.anatomical_structure chemistry Fluorouracil Delayed-Action Preparations Nanoparticles Skin cancer 0210 nano-technology Biotechnology medicine.drug Biomedical engineering |
Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 163:223-239 |
ISSN: | 0939-6411 |
Popis: | In the present study, combinatorial nanostructured lipid carrier gel of 5-fluorouracil and resveratrol was formulated, optimized and characterized to enhance permeation in between epidermis and dermis layers of the skin to obtain a synergistic effect against skin cancer. After extensive trials, a newly modified emulsiosonication method was developed and additionally, for the first time, stability studies were done in the beginning to optimize formulation technique, which exhibited two major benefits simultaneously; first, it provided best-optimized technique for preparation of combinatorial lipid-nanosystem, and secondly, it also demonstrated a detailed report card of durability of formulations. In vitro release study showed a significantly improved, slow and prolonged release of drugs from the optimized lipid-nanosystem (***p 0.05), which followed non-Fickian Higuchi kinetics. Besides, mechanism of skin permeation enhancement study, dermatokinetic assessment, and depth analysis of optimized formulation on skin exhibited improved permeation and well distribution of drugs up to the dermis layer of skin. Moreover, combinatorial linogel possessed significantly greater efficacy (**p 0.01) on the A431 cell line, as compared to the conventional formulation. Thus, findings revealed that modified method of preparation for dual drug-loaded lipid-nanosystem lead to the production of a stable formulation that also improved the retention of both 5-fluorouracil and resveratrol in between the epidermis and dermis region of skin thereby helping in the management and treatment of skin cancer. |
Databáze: | OpenAIRE |
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